Male dogs and cats were immunized against LHRH in order to evaluate the feasibility of an immunological approach to pet contraception. In the first study, dogs were immunized with 100, 500, or 2500 micrograms of LHRH conjugated to tetanus toxoid. A significant decline in serum testosterone (T) levels was observed in all immunized dogs, reaching castration levels in some animals by Week 4 and remaining suppressed in all the immunized dogs through the course of the study. Testicular histology suggested arrest of spermatogenesis (infertility). The effects of "immunological castration" were reversible (study 2): steroidogenesis suppressed by "immunological castration" was restored as antibody titers declined. Effective antibodies were rapidly reinduced in dogs by a single injection of LHRH1-TT. In contrast, the level of antibodies induced in male cats (study 3) was not sufficient for "immunological castration." The conclusion was that active immunization against LHRH could provide a cost-effective, nonsurgical, reversible means to control the fertility of companion animals.

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Male rats and rabbits were immunized against gonadotropin-releasing hormone (GnRH) conjugated to tetanus toxoid (GnRH10-TT) using only materials approved for humans. Testosterone (T)-releasing implants or the long-lasting T ester testosterone-17-trans-4-n-butyl-cyclohexane carboxylate (TE) was used as supplemental androgen for maintaining libido. Immunization against GnRH10-TT effectively suppressed fertility (spermatogenesis) in rats and rabbits. Neither T nor TE administration restored fertility. Both androgens were effective in maintaining normal libido in rats. TE, which is not hydrolyzed in rabbits, was less effective in maintaining normal ejaculatory behavior in this species. Active immunization against GnRH could be a convenient and cost-effective method of fertility control in males.

Active immunization against LHRH conjugated to TT at the 1-position has potential as a fast, convenient method of male contraception.

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